Williams Kenneth R, Colangelo Christopher M, Hou Lin, Chung Lisa, Belcher Justin M, Abbott Thomas, Hall Isaac E, Zhao Hongyu, Cantley Lloyd G, Parikh Chirag R
W.M. Keck Foundation Biotechnology Laboratory, Yale University School of Medicine, New Haven, USA.
Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, USA.
Proteomics Clin Appl. 2017 Jul;11(7-8). doi: 10.1002/prca.201600132. Epub 2017 Mar 31.
Development of delayed graft function (DGF) following kidney transplant is associated with poor outcomes. An ability to rapidly identify patients with DGF versus those with immediate graft function (IGF) may facilitate the treatment of DGF and the research needed to improve prognosis. The purpose of this study was to use a Targeted Urine Proteome Assay to identify protein biomarkers of delayed recovery from kidney transplant.
Potential biomarkers were identified using the Targeted Urine Proteome (MRM) Assay to interrogate the relative DGF/IGF levels of expression of 167 proteins in urine taken 12-18 h after kidney implantation from 21 DGF, 15 SGF (slow graft function), and 16 IGF patients. An iterative Random Forest analysis approach evaluated the relative importance of each biomarker, which was then used to identify an optimum biomarker panel that provided the maximum sensitivity and specificity with the least number of biomarkers.
Four proteins were identified that together distinguished DGF with a sensitivity of 77.4%, specificity of 82.6%, and AUC of 0.891. This panel represents an important step toward identifying DGF at an early stage so that more effective treatments can be developed to improve long-term graft outcomes.
肾移植后延迟移植肾功能（DGF）的发生与不良预后相关。快速区分DGF患者与移植肾功能立即恢复（IGF）患者的能力，可能有助于DGF的治疗以及改善预后所需的研究。本研究的目的是使用靶向尿液蛋白质组分析来鉴定肾移植后恢复延迟的蛋白质生物标志物。
使用靶向尿液蛋白质组（MRM）分析来鉴定潜在的生物标志物，以检测21例DGF患者、15例移植肾功能缓慢恢复（SGF）患者和16例IGF患者在肾移植术后12 - 18小时尿液中167种蛋白质的相对DGF/IGF表达水平。采用迭代随机森林分析方法评估每个生物标志物的相对重要性，然后用于确定一个最佳生物标志物组合，该组合能以最少的生物标志物数量提供最大的敏感性和特异性。
鉴定出四种蛋白质，它们共同区分DGF的敏感性为77.4%，特异性为82.6%，曲线下面积（AUC）为0.891。该组合代表了朝着早期识别DGF迈出的重要一步，以便能够开发出更有效的治疗方法来改善长期移植结局。
